tbuckley/cabot-search huggingface dataset:
When I use a word . . . . Medical words of 1952—a jubilee celebration
Authors: Jeffrey K Aronson
Journal: BMJ (2022)

The words whose first recorded instances, their lexicographic birthdays, are recorded in the <i>Oxford English Dictionary (OED)</i> as having occurred in 1952, 70 years ago, tell us something about events at that time. They suggest in particular that 1952 marked the start of an important period of drug discovery. Disorders and pathological features that were first noticed in the <i>OED</i> in 1952 included acatalasia, agammaglobulinaemia, Christmas disease, ganglionopathies, hypsarrhythmias associated with infantile spasms, microangiopathy, mucopolysaccharidosis, neovascularization, and Takayasu’s arteritis. The ways in which computers influence our lives today was also presaged in 1952, by the appearance of the term “information technology,” as well as terms such as “computer programming.”
Predictors of complication after groin dissection: A contemporary experience.
Authors: Ghader Jamjoum, Thea Araji, Diana Nguyen, Ari N. Meguerditchian
Journal: Journal of Clinical Oncology (2022)

e21531 Background: Inguinal lymphadenectomy (ILND) has historically been associated with significant morbidity. The advent of sentinel node biopsy and selective dissection protocols have significantly decreased the frequency with which ILND is performed, reserving it for complex, recurrent disease. The study objective is to obtain contemporary morbidity rates for this complex procedure and to identify potentially preventable risk factors. Methods: Retrospective review of medical charts for all superficial, deep, and combination groin dissections performed for melanoma, sarcoma, and other rare cancers at a single, high-volume academic center between 01/2007 and 12/2020. Data points collected: patient, disease, surgery characteristics, and cancer outcomes. Outcome of interest: any complication within 30 days of surgery. Complications: wound infection, wound necrosis/disruption, seroma, drainage procedure, hematoma, lymphedema, and other. Multivariate logistic regression performed using SAS Enterprise 9.4. Results: : 139 cases were identified; type of dissection was 89, 12, and 38 for superficial, deep, and combined respectively. Melanoma accounted for 84.9% of cases, sarcoma for 8.6%. 56.1% of patients had an adverse postoperative event within 30 days. The majority of patients did not have a history of smoking, diabetes, cardiovascular disease, hypothyroidism, or radiation therapy. 61.2% were recurrent cancer cases with 56.8%, 19.4%, and 23.7% being clinically evident, radiological-only, and sentinel node positive disease respectively. Type and frequency of complications is reported in Table. Increasing age (OR: 1.04, 95CI: 1.01-1.07, P &lt; 0.01) and number of positive lymph nodes harvested (OR: 1.22, 95CI: 1.00-1.50, P = 0.05) were associated with more complications. Deep dissection showed lower likelihood of complications than those with superficial (OR: 0.15, 95CI: 0.03-0.84, P &lt; 0.05). Conclusions: A number of risk factors for complications were identified opening up opportunities for preventative intervention such as prehabilitation, use of frailty score, and neo-adjuvant therapy. Deep vein thrombosis, abscess, general deterioration, neuropathic pain, numbness. Frequency by occurrence, not patient. [Table: see text]
E-Consent – an innovative solution to maintain recruitment momentum in clinical trials during the COVID-19 pandemic
Authors: R. Almeida-Magana, J. Grierson, H. Maroof, R. Clow, E. Dineen, T. Al-Hammouri, N. Muirhead, C. Brew-Graves, J. Kelly, G. Shaw
Journal: European Urology (2022)
PROOF 301: A multicenter, open-label, randomized, phase 3 trial of infigratinib versus gemcitabine plus cisplatin in patients with advanced cholangiocarcinoma with an <i>FGFR2</i> gene fusion/rearrangement.
Authors: Ghassan K. Abou-Alfa, Ivan Borbath, Lipika Goyal, Angela Lamarca, Teresa Macarulla, Do-Youn Oh, Sameek Roychowdhury, Saeed Sadeghi, Rachna T. Shroff, Ai Li, Jose Soto, Francesca Avogadri, Carl L. Dambkowski, Milind M. Javle
Journal: Journal of Clinical Oncology (2022)

TPS4171 Background: First-line treatment options are limited for patients with advanced cholangiocarcinoma (CCA). Genetic alterations in the fibroblast growth factor receptor ( FGFR) gene play an important role in CCA. FGFR gene fusions/rearrangements are present in 10–16% of intrahepatic CCA and may predict tumor sensitivity to FGFR inhibitors. Infigratinib (BGJ398) is a potent, orally bioavailable, selective, ATP-competitive, small-molecule tyrosine kinase inhibitor of FGFRs that showed promising clinical activity and a manageable adverse event profile in a phase 2 study in patients with previously treated, unresectable locally advanced/metastatic CCA with an FGFR2 gene fusion/rearrangement. The multicenter, open-label, randomized, controlled phase 3 PROOF 301 trial is evaluating infigratinib vs standard-of-care gemcitabine + cisplatin as first-line treatment for patients with advanced/metastatic or inoperable CCA with an FGFR2 gene fusion/rearrangement. Methods: Approximately 300 patients ≥18 years of age with histologically or cytologically confirmed, advanced/metastatic or inoperable CCA with an FGFR2 gene fusion/rearrangement (confirmed by central laboratory) are randomized 2:1 to oral infigratinib 125 mg once daily for the first 21 days of a 28-day treatment cycle vs intravenous standard gemcitabine (1000 mg/m 2 ) + cisplatin (25 mg/m 2 ) on days 1 and 8 of a 21-day cycle. Randomization will be stratified by unresectable locally advanced vs metastatic disease, geographic region, prior neoadjuvant/adjuvant treatment vs none, and receipt of up to 1 cycle of gemcitabine-based chemotherapy for unresectable locally advanced/metastatic disease prior to randomization vs none. Treatment will continue until confirmed progressive disease by blinded independent central review (BICR), intolerance, withdrawal of informed consent, or death. Patients on the gemcitabine + cisplatin arm who develop disease progression, confirmed by BICR, can cross-over to receive infigratinib. The primary endpoint is progression-free survival (PFS, RECIST v1.1), confirmed by BICR. Secondary endpoints include overall survival, PFS (investigator determined), overall response rate, best overall response, disease control rate, duration of response (BICR and investigator determined), and the type, frequency, and severity of adverse events (AEs) and serious AEs. PFS after subsequent therapy (PFS2), quality of life, pharmacokinetics and other exploratory genetic alterations/biomarkers will also be evaluated. Trial enrollment is ongoing in the US, EU, and APAC (including Australia). The Data Monitoring Committee last reviewed the trial in December 2021. Clinical trial information: NCT03773302.
The prognostic value of the number of positive targeted cores in men with positive multiparametric magnetic resonance imaging of the prostate. Results from a large, multi-institutional series
Authors: A. Stabile, E. Mazzone, G. Gandaglia, G. Ploussard, R-G. Rahota, M. Valerio, R. Campi, A. Mari, A. Mattei, G. Marra, J.B. Beavaul, M. Roumiguiè, L. Afferi, M. Moschini, P. Gontero, R. Van Den Bergh, J. Zhuang, H. Tuo, N. Fossati, F. Montorsi, A. Briganti
Journal: European Urology (2022)
The diagnostic issue of variant histologies in bladder cancer: Does the centre have an impact in detection accuracy?
Authors: A. Cimadamore, C. Lonati, E. Di Trapani, O. De Cobelli, M. Rink, S. Zamboni, C. Simeone, F. Soria, A. Briganti, F. Montorsi, A. Antonelli, R.J. Karnes, R. Sanchez-Sala, R. Hurle, C. Poyet, D. D'Andrea, S.F. Shariat, S. Francavilla, W. Krajewski, E. Laukhtina, E. Xylinas, M. Rouprêt, R. Montironi, M. Moschini
Journal: European Urology (2022)
Effect of docetaxel (D) use on survival outcomes in patients with metastatic castration-sensitive prostate cancer (mCSPC) treated with novel hormonal therapies (NHTs): A meta-analysis.
Authors: Deniz Can Guven, Nicolas Sayegh, Nishita Tripathi, Mustafa Erman, Neeraj Agarwal, Umang Swami
Journal: Journal of Clinical Oncology (2022)

5079 Background: ARASENS and PEACE-1 trials have shown that the addition of NHTs to D + androgen deprivation therapy (ADT) improves overall survival (OS) outcomes in mCSPC. However, whether a true synergism is present with using NHT+ADT+D is unknown due to the lack of a trial testing the efficacy of adding D to the NHT+ADT backbone. Our objective was to evaluate the survival outcomes with NHTs according to D use in mCSPC. Methods: The literature search was done from PubMed and Embase databases to identify published studies until February 12 th , 2022 for meta-analysis. The MeSH search terms were “castration-sensitive prostate cancer” OR “hormone-sensitive prostate cancer” OR “hormone-naïve prostate cancer” AND “abiraterone” OR “apalutamide” OR “enzalutamide” OR “darolutamide”. The target outcome measures were progression-free survival (PFS) and OS. Generic inverse-variance method with a fixed-effects model was used, with hazard ratios with 95% two-sided confidence intervals (CI) as the principal summary measure (Review Manager software, version 5.3, The Nordic Cochrane Center, The Cochrane Collaboration, Copenhagen, Denmark). P values below 0.05 were considered statistically significant. Results: The literature search retrieved a total of 2565 records. Six phase III studies encompassing 6701 patients evaluating survival outcomes with NHTs in mCSPC (TITAN, ARCHES, ENZAMET, LATITUDE, STAMPEDE Abi- M1, and PEACE-1) were included after filtering of the available records. Results summarized in below table. In the combined analysis, the addition of NHTs to standard of care (SOC) improved PFS and OS. PFS benefit with NHTs was similar in studies (or study subgroups) with or without D use. However the relative OS benefit with a NHT was higher in studies (or study subgroups) without D than studies permitting D (concurrent or sequential). Conclusions: In this meta-analysis, the PFS and OS benefit with NHT in mCSPC was observed independent of D use. A randomized phase III study comparing D+NHT+ADT with NHT+ADT is needed to evaluate the contribution of D to survival outcomes in patients with mCSPC receiving treatment with NHT+ADT. [Table: see text]
Treatment of patients with hematological malignancies and left-ventricular assisted device (LVAD) managed cardiomyopathy.
Authors: Frances Natalia Cervoni-Curet, Adan Rios, Binoy Yohannan
Journal: Journal of Clinical Oncology (2022)

e19581 Background: An estimated 2-3% of individuals who undergo advanced heart failure therapies, such as left ventricular assist devices (LVAD) or orthotopic heart transplantation (OHT), have an antineoplastic-related cardiomyopathy. We investigated the incidence and clinical outcomes of non-ischemic or dilated cardiomyopathies on LVAD patients who have been diagnosed with lymphomas or leukemias in our institution between years 2015 - 2022. Methods: We found four cases of patients with newly diagnosed hematological malignancy who had existing underlying LVAD-dependent cardiomyopathy in our center. One patient was excluded due to loss to follow up. The other three patients were treated in the heart failure unit while concurrently managed by LVAD specialists. One patient required administration of continuous 72hr-infusion of doxorubicin to minimize the risk of right-sided ventricular failure. The response to treatment was assessed with use of PET-CT scans, bone marrow biopsies and serological markers per standard of care guidelines. Results: The median age was 54.6 years. Two were African Americans, one Caucasian and one Hispanic (lost to follow up). All patients were males. Of these four individuals, two were diagnosed with Non-Hodgkin Lymphomas (one Peripheral T-cell lymphoma, one Diffuse Large B-cell lymphoma), one with Chronic Lymphocytic Leukemia (CLL) and one with Acute Promyelocytic Leukemia (APL). Three patients completed or have ongoing chemotherapeutic treatment. All have achieved complete remission (CR 3/3) of their diseases. Conclusions: To date, there is no significant volume of data showing the administration of chemotherapy on patients with concurrent LVAD-dependent cardiomyopathies. The Peripheral T-cell lymphoma patient received anthracycline therapy via a continuous 72-hour infusion with close LVAD monitoring at the heart failure unit. After completion of total 6 cycles in 2021, he still is in complete remission. Our CLL patient, has also completed 5 cycles of rituximab and venetoclax while also maintaining disease remission. The APL patient has completed 5 cycles of arsenic trioxide and ATRA with also a complete remission of his leukemia. LVAD-dependent cardiomyopathy patients concurrently diagnosed with malignant hematological diseases, can be considered for treatment with antineoplastic therapies. Durable remission rates can be achieved while undergoing aggressive cardiovascular care.
Evaluating the role of stents on strings and other non cystoscopic removal methods in children: A systematic review on behalf of the European Association of Urology (EAU) Young Academic Urology (YAU) Urolithiasis Working Party
Authors: P. Juliebø-Jones, V. Massella, A. Pietropaolo, J. Haugland, I. Mykoniatis, B.K. Somani
Journal: European Urology (2022)
Automatic 3D+t four-chamber CMR quantification of the UK biobank: integrating imaging and non-imaging data priors at scale
Authors: Yan Xia, Xiang Chen, Nishant Ravikumar, Christopher Kelly, Rahman Attar, Nay Aung, Stefan Neubauer, Steffen E. Petersen, Alejandro F. Frangi
Journal: Medical Image Analysis (2022)

Accurate 3D modelling of cardiac chambers is essential for clinical assessment of cardiac volume and function, including structural, and motion analysis. Furthermore, to study the correlation between cardiac morphology and other patient information within a large population, it is necessary to automatically generate cardiac mesh models of each subject within the population. In this study, we introduce MCSI-Net (Multi-Cue Shape Inference Network), where we embed a statistical shape model inside a convolutional neural network and leverage both phenotypic and demographic information from the cohort to infer subject-specific reconstructions of all four cardiac chambers in 3D. In this way, we leverage the ability of the network to learn the appearance of cardiac chambers in cine cardiac magnetic resonance (CMR) images, and generate plausible 3D cardiac shapes, by constraining the prediction using a shape prior, in the form of the statistical modes of shape variation learned a priori from a subset of the population. This, in turn, enables the network to generalise to samples across the entire population. To the best of our knowledge, this is the first work that uses such an approach for patient-specific cardiac shape generation. MCSI-Net is capable of producing accurate 3D shapes using just a fraction (about 23% to 46%) of the available image data, which is of significant importance to the community as it supports the acceleration of CMR scan acquisitions. Cardiac MR images from the UK Biobank were used to train and validate the proposed method. We also present the results from analysing 40,000 subjects of the UK Biobank at 50 time-frames, totalling two million image volumes. Our model can generate more globally consistent heart shape than that of manual annotations in the presence of inter-slice motion and shows strong agreement with the reference ranges for cardiac structure and function across cardiac ventricles and atria.
Characterization of industry relationships in oncology.
Authors: Rebecca A. Harrison, Nazanin Majd, Margaret O. Johnson, Diana L. Urbauer, Vinay K. Puduvalli, Mustafa Khasraw
Journal: Journal of Clinical Oncology (2022)

11025 Background: Collaborative relationships between academic oncology and the pharmaceutical industry are essential for therapeutic development in oncology. Despite this, formal training and mentorship in developing productive industry collaborations are not routinely included in oncology training. Since little research has been done to characterize and optimize the efficiency of these relationships, we sought to better understand the nature of such collaborations in order to identify areas for optimization. Methods: An electronic survey was administered to 1000 randomly selected ASCO members. The survey included 23 questions eliciting demographic and practice information, and 26 questions eliciting respondents’ views around oncology-industry collaborations. Survey results were analyzed using descriptive statistics. Results: There were 225 survey respondents. Most were from the United States (70%), worked at an academic institution (60.1%), worked in medical oncology (81.2%), and had an active relationship with industry (85.8%). 26.7 % of respondents reported difficulty establishing a relationship with industry collaborators. Many relied on federal (39.5%) or departmental (30.2%) funding to supplement their research ventures. Partnerships were initiated by the respondents themselves (34.6%) or industry partners (31.9%) with similar frequency, whereas institutional affiliations (15.7%) and collaborative groups (5.8%) were reported as less common means for establishing collaborations. The majority (85.3%) of respondents stated these collaborations were of importance to their career. Inclusion in industry sponsored trials (71.1%) and commitment to research funding (66.3%) were considered early signs of a productive relationship, whereas lack of effective communication (86.1%) or little engagement by senior industry leadership (63.1%) were early red flags. Most respondents (75%) did not report having had mentorship in developing these relationships. Scientific integrity was generally thought to be preserved (92%) and there was little concern over the quality of the collaborative product (95%). Many shared concern over potential conflict of interest if a compensated relationship promoted an industry product for clinical care/research (60%), yet also stated these relationships did not shape their interactions with patients (67%). Conclusions: This study provides novel data characterizing the nature of collaborative industry-academia relationships in oncology. While respondents considered these collaborations an important part of clinical and academic oncology, formal education or mentorship around these relationships is rare. Further study exploring the structure of effective industry collaborations, optimizing methods to provide education in this area at all career stages, navigating conflict of interest issues in these relationships, and understanding industry perspectives is warranted.
INSP-13. Malignant networks in brain tumors: from basic discoveries to clinical implications
Authors: Frank Winkler
Journal: Neuro-Oncology (2022)

Abstract Integration into communicating tumor cell networks is a way how the entire brain tumor organism can progress in the brain, and resist therapies. It started with our discovery of ultra-long membrane protrusions, tumor microtube (TM), in tumor cells from glioblastomas and other incurable adult and pediatric glioma entities (Osswald et al., Nature 2015). These TMs are used for early brain invasion, and later interconnect single tumor cells to communicating and resistant multicellular networks, but also glioma cells to neurons in the brain, with neuron-glioma synapses stimulating glioma progression (Venkataramani et al., Nature 2019). Increasing formation of these homotypic and heterotypic networks is seen with increasing glioma malignancy: lowest in low-grade oligodendrogliomas, and highest in glioblastomas and K27M mutated gliomas. The genetic reduction of GAP-43, a crucial neurodevelopmental factor that drives TM formation and function, not only deprived glioblastoma cells from the ability to form functional tumor networks, but also made radiotherapy much more effective, by and large eradicating experimental tumors from the mouse brain, which is typically not possible with radiotherapy alone. Consistent with the concept of tumor cell resilience by network integration, radiotherapy and also chemotherapy (Weil et al., Neuro-Oncology 2017) preferentially killed the unconnected glioblastoma cells, leaving the tumor cell networks largely intact. Damage to the tumor network by surgical measures induced a self-healing response. Taken together, integration into multicellular, highly functional, communicating and resilient networks is not only a feature of the nervous system, but also of incurable, most aggressive brain tumors. In this talk, clinical concepts that originate from these discoveries are presented, including a network disconnection strategy currently tested in the German MecMeth trial (EudraCT2021-000708-39), and the AMPAR inhibitor perampanel as a potential inhibitor of neuron-glioma synapses. Furthermore, new basic and translational developments in the field of brain tumor networks are presented and discussed.
Evaluating the state of the science for adeno-associated virus integration: An integrated perspective
Authors: Denise E. Sabatino, Frederic D. Bushman, Randy J. Chandler, Ronald G. Crystal, Beverly L. Davidson, Ricardo Dolmetsch, Kevin C. Eggan, Guangping Gao, Irene Gil-Farina, Mark A. Kay, Douglas M. McCarty, Eugenio Montini, Adora Ndu, Jing Yuan
Journal: Molecular Therapy (2022)

On August 18, 2021, the American Society of Gene and Cell Therapy (ASGCT) hosted a virtual roundtable on adeno-associated virus (AAV) integration, featuring leading experts in preclinical and clinical AAV gene therapy, to further contextualize and understand this phenomenon. Recombinant AAV (rAAV) vectors are used to develop therapies for many conditions given their ability to transduce multiple cell types, resulting in long-term expression of transgenes. Although most rAAV DNA typically remains episomal, some rAAV DNA becomes integrated into genomic DNA at a low frequency, and rAAV insertional mutagenesis has been shown to lead to tumorigenesis in neonatal mice. Currently, the risk of rAAV-mediated oncogenesis in humans is theoretical because no confirmed genotoxic events have been reported to date. However, because insertional mutagenesis has been reported in a small number of murine studies, there is a need to characterize this genotoxicity to inform research, regulatory needs, and patient care. The purpose of this white paper is to review the evidence of rAAV-related host genome integration in animal models and possible risks of insertional mutagenesis in patients. In addition, technical considerations, regulatory guidance, and bioethics are discussed.
LiKidMiRs: Unveiling the diagnostic potential of liquid biopsy-based circulating microRNAs in renal cell tumors
Authors: C. Jeronimo, J.P. Sequeira, V. Constâncio, S. Salta, J. Lobo, C. Carvalho-Maia, I. Braga, R. Henrique
Journal: European Urology (2022)